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Annals of Biomedical Engineering

, Volume 44, Issue 2, pp 276–286 | Cite as

Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating

  • Natalie Artzi
  • Abraham R. TzafririEmail author
  • Keith M. Faucher
  • Geoffrey Moodie
  • Theresa Albergo
  • Suzanne Conroy
  • Scott Corbeil
  • Paul Martakos
  • Renu Virmani
  • Elazer R. Edelman
Medical Stents: State of the Art and Future Directions

Abstract

The long held assumption that sustained drug elution from stent coatings over weeks to months is imperative for clinical efficacy has limited the choice for stent coating materials. We developed and evaluated an omega-3 fatty acid (O3FA) based stent coating that is 85% absorbed and elutes 97% of its Sirolimus analog (Corolimus) load within 8d of implantation. O3FA coated stents sustained drug levels in porcine coronary arteries similarly to those achieved by slow-eluting durable coated Cypher Select Plus Stents and with significantly lower levels of granuloma formation and luminal stenosis. Computational modeling confirmed that diffusion and binding constants of Corolimus and Sirolimus are identical and explained that the sustained retention of Corolimus was facilitated by binding to high affinity intracellular receptors (FKBP12). First in man outcomes were positive—unlike Cypher stents where late lumen loss drops over 6 month, there was a stable effect without diminution in the presence of O3FA. These results speak to a new paradigm whereby the safety of drug eluting stents can be optimized through the use of resorbable biocompatible coating materials with resorption kinetics that coincide with the dissociation and tissue elimination of receptor-bound drug.

Keywords

Drug eluting stents Sirolimus analogs Computational modeling 

Notes

Acknowledgments

This study was supported in part by grants from the NIH (R01 GM-49039) to ERE and in part by support of animal work and preclinical studies at MIT, CBSET and CVPath. ERE and RV are paid consultants to Atrium. Coauthors KMF, GM, TA, PM, S. Conroy and S. Corbeil are employees of Atrium Medical Corporation and provided input into the study design and editorial input into the writing of the manuscript. Data collection, analysis and interpretation of animal and computer experiments were all performed independent of input from Atrium Medical Corporation. The decision to submit the paper for publication came from joint discussions between Atrium Medical management and all authors. The authors would like to acknowledge Alicia Dale, Roger Labrecque and Jessica Mayer from Atrium Medical Corporation for assistance in executing experimental work to support this publication.

Supplementary material

10439_2015_1435_MOESM1_ESM.pdf (870 kb)
Supplementary material 1 (PDF 871 kb)

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Copyright information

© Biomedical Engineering Society 2015

Authors and Affiliations

  • Natalie Artzi
    • 1
    • 2
  • Abraham R. Tzafriri
    • 1
    • 3
    Email author
  • Keith M. Faucher
    • 4
  • Geoffrey Moodie
    • 4
  • Theresa Albergo
    • 4
  • Suzanne Conroy
    • 4
  • Scott Corbeil
    • 4
  • Paul Martakos
    • 4
  • Renu Virmani
    • 5
  • Elazer R. Edelman
    • 1
    • 6
  1. 1.Institute for Medical Engineering and ScienceMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of Anesthesiology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.Department of Applied ScienceCBSET Inc.LexingtonUSA
  4. 4.MAQUET Vascular Systems (Formerly Atrium Medical Corporation)MerrimackUSA
  5. 5.CV Path InstituteGaithersburgUSA
  6. 6.Cardiovascular Division, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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